Summary

-Intranasal budesonide therapy may lead to improved symptoms and sleep study findings in
children with mild obstructive sleep apnea with and without allergic rhinitis that would not
be treated with T&A. The aim of the study is to conduct a randomized double blind cross-over
trial comparing the effect of once a day intranasal budesonide therapy vs. placebo in
children with mild sleep apnea that would not be candidates for T&A.

Additional Information

Untreated OSAS can result in serious morbidity, primarily affecting neurobehavioral and
cardiovascular systems.
The severity of OSAS is only partially related to the adenoid and tonsillar size. While
adenotonsillectomy (T&A) is the most common treatment for children with OSAS, this approach
is reserved for children whose apnea/hypopnea index in the overnight sleep study exceeds a
critical value. However, there is no consensus on the appropriate management of children
with AHI >1 but <7 events/hour of sleep. These children constitute between 4-6% of all
children and there are no alternative long-term interventions, and therefore a medical
approach that obviates surgery, yet leads to substantial amelioration in the
sleep-disordered breathing is critically needed.
Anti-inflammatory agents like intra-nasal corticosteroids are considered an effective
treatment for children with allergic rhinitis. However, only one study has been conducted so
far, and has examined the effect of intranasal corticosteroids, in pediatric patients with
florid OSAS. Thus, no studies are available on topical steroids in patients with OSAS
severity that would not justify T&A.
Our leading hypothesis is:
- Intranasal budesonide therapy may lead to improved symptoms and polysomnographic findings
in children with OSAS with and without allergic rhinitis that would not be treated with T&A.
Subjects And Methods Study population Specific Aim. Up to 100 children will be recruited
from all pediatric patients referred for evaluation of snoring and who underwent clinical
evaluation, lateral neck x-ray, and an overnight sleep study at the Kosair Children's
Hospital Sleep Medicine and Apnea Center.
Study Design Specific Aim: After informed consent is obtained from the parents, children
fulfilling the entry criteria will be randomized using a table of random numbers that will
be provided by Astra-Zeneca. Patients will be allocated into parallel treatment groups with
simple randomization in blocks of 4 in a double blind fashion, according to the
randomization procedure delineated by Astra-Zeneca All patients will complete a
questionnaire regarding symptoms of snoring and allergic rhinitis symptoms prior to starting
the study. One of the groups will start a-6 week course of either nasal topical budesonide
(32 mcg/puff/nostril to both nostrils (total of 64 mcg), once a day or placebo. Parents will
be instructed to give the drug at bedtime. Parents will be contacted weekly by the
investigators to determine whether the study drug is being given as prescribed. When unable
to contact parents by phone, they will be sent a follow up letter accompanied with the
weekly questionnaire and a postage-paid return envelope. After 6 weeks, patients will have
an overnight sleep study, lateral neck x-ray, and they will fill in a questionnaire
regarding snoring and rhinitis symptoms.. At the end of the 6 weeks, patients will start a
6-week course with the compound that they were not receiving during the 1st phase of the
study. All the outcome endpoints will be assessed again upon completion of the 2nd 6-week
course.
The overall rationale for this schedule is as follows:
We are aiming to assess whether intranasal budesonide is effective in ameliorating
sleep-disordered breathing in these children. Therefore, we aim to maximize the number of
children receiving intranasal budesonide. This is achieved in the above experimental scheme
since all children will receive 6 weeks of the therapy, either at the onset of their 12-week
participation or after 6 weeks (for those who will be randomized to placebo treatment in the
initial 6 weeks). The rationale for a 6-week duration period is that we anticipate that the
reduction in adenoid volume will be a slow process that requires between 3-6 weeks to reach
its peak effect. We also wish to determine whether cessation of intranasal budesonide is
associated with exacerbation of the SDB. To this effect, the group of children who were
initially treated with budesonide for 6 weeks will provide the data towards answering this
important question. We anticipate that rebound increase in severity will occur but may take
several weeks to manifest since the incremental growth of adenoid tissue will also take
time.
Both nasal-budesonide and placebo inhalers will be provided in identical containers by the
drug manufacturer. The appearance and smell of the budesonide and placebo will be
indistinguishable. The investigators will not be aware of the compound being used. The codes
for each patient will be kept by Astra-Zeneca. If any adverse event develops, the patients
will be withdrawn from the study and followed clinically to assess overall clinical course.
Experimental Protocols
Symptoms questionnaire All patients will fill a snoring and symptom questionnaire.
Lateral Neck X-Rays This will be performed using standard techniques in the Radiology
Department at KCH.
Overnight Polysomnography All children participating in the study will be
polysomnographically studied before inclusion as part of their routine clinical evaluation.
In addition, they will undergo 2 additional sleep studies, each at the end of the 6-week
intervention period of the study.
Statistics A sample size of 50 patients per arm in this parallel design study was estimated
based on an alpha error of 0.05, beta error of 0.2, a baseline mean apnea hypopnea index
(AHI) of 3, with an SD of 1.5, and a potential decrease in AHI by 20%. In addition, such
number of subjects would allow for detection of a 30% improvement in rhinitis scores. Even
if attrition occurs, 40 subjects per arm will be sufficient assuming a 30% improvement in
AHI according to sleep study. This design and number will also permit accurate
determination of rebound exacerbation following transition from budesonide to placebo in
half the subjects. (see above). Results will be expressed as the mean +/- SEM. To assess
treatment effectiveness, paired t-tests will be used to compare normally distributed
variables.
Potential Risks Nasal budesonide (Rhinocort Aqua, AstraZeneca) is generally well tolerated..
The most commonly reported adverse events( more then 2%) for Rhinocort Aqua and vehicle
placebo (a formulation with no active drug) respectively were: epistaxis (nosebleed) - 8
percent vs 5 percent; pharyngitis (sore throat) - 4 percent vs 3 percent; bronchospasm 2
percent vs 1 percent; nasal irritation - 2 percent vs <1 percent; and coughing - 2 percent
vs <1 percent.
Rare adverse events reported include: nasal septum perforation, pharynx disorders (throat
irritation or pain, swollen throat, burning throat, itching throat, angioedema, anosmia and
palpitations. Even though, studies have shown detectable adrenal suppression with intranasal
steroids administration,30 intranasal budesonide 200 µg once daily has been found to have no
effects on 24 hour, or fractionated cortisol profiles in serum or urine.31 And although
transient growth suppression have been reported with medium to high dose inhaled steroids,
no similar side effects were reported during clinical studies with intranasal budesonide.
Furthermore, the addition of intranasal budesonide therapy to medium dose of inhaled
budesonide in children with asthma for approximately 24 months had no significant effect on
final adult height.32
Potential Benefits It is possible that the participants will have improvements in the
severity of their OSAS and their snoring severity during nasal budesonide therapy.
The information obtained in our study, will help to define the role of nasal budesonide
intervening in the pathophysiology of OSAS, and the potential role of nasal budesonide as a
nonsurgical therapy for children with otherwise mild OSAS who would not be considered as
candidates for T&A.
Significance of Research For children with OSAS that is too mild to justify T&A surgery,
Intranasal therapy with budesonide may become a safe and effective new therapy aiming to
minimize the morbidity associated with OSAS in children.

Trial information was received from ClinicalTrials.gov and was last updated in November 2007.

Information provided to ClinicalTrials.gov by University of Louisville.